Extracellular secretion of products is the major mechanism by which Gram-negative pathogens communicate with and intoxicate host cells. Vesicles released from the envelope of growing bacteria serve as secretory vehicles for proteins and lipids of Gram-negative bacteria. Vesicle production occurs in infected tissues and is influenced by environmental factors. Vesicles play roles in establishing a colonization niche, carrying and transmitting virulence factors into host cells, and modulating host defense and response. Vesicle-mediated toxin delivery is a potent virulence mechanism exhibited by diverse Gram-negative pathogens. The biochemical and functional properties of pathogen-derived vesicles reveal their potential to critically impact disease.In nearly every case, virulence factors of Gram-negative pathogens are secreted products that enhance the survival of the bacteria and/or damage the host. Secretion of virulence factors by Gram-negative pathogens is complicated by the fact that the bacterial envelope consists of two lipid bilayers, the inner and outer membrane, and the periplasm in between. Gram-negative pathogens have developed many strategies, some specific to pathogens, to enable active virulence factors to gain access to the extracellular environment, typically the tissues or bloodstream of the host organism (Henderson et al. 2004). The Type II and Type V secretion systems are two-step processes in which proteins are transported first through the inner membrane (IM) and then through the outer membrane (OM). For secretion via the Type I, Type III, and Type IV secretion systems, the material is transferred directly into the extracellular milieu or into another cell. The Type III system is specific for the transport of factors by pathogenic bacteria. All of these secretion systems secrete individual proteins or small complexes. This review examines secretion via OM vesicles, a distinct "Type VI" mechanism that enables bacteria to secrete a large, complex group of proteins and lipids into the extracellular milieu.Both pathogenic and nonpathogenic species of Gram- Vesicles are a means by which bacteria interact with prokaryotic and eukaryotic cells in their environment. Some of the best-characterized vesicles are those produced by pathogens. Biochemical analysis and functional characterization of pathogen-derived outer membrane vesicles demonstrate that this secretory pathway has been usurped by pathogens for the transport of active virulence factors to host cells (Table 1). Naturally produced OM vesicles from pathogenic bacteria contain adhesins, toxins, and immunomodulatory compounds, and they directly mediate bacterial binding and invasion, cause cytotoxicity, and modulate the host immune response. By participating in such diverse aspects of the host-pathogen interaction, OM vesicles are potent bacterial virulence factors.
Formation of bacterial OM vesiclesNaturally produced bacterial vesicles are discrete, closed OM blebs produced by growing cells, not products of cell lysis or cell death (Mug-Opstelte...